Core Insights - Immutep Limited reports significant operational progress in the TACTI-004 Phase III trial for eftilagimod alfa (efti) in combination with KEYTRUDA and chemotherapy for advanced non-small cell lung cancer [1][5] Group 1: Trial Progress - The TACTI-004 trial has enrolled 289 patients, which is over 38% of the targeted 756 patients, with recruitment continuing at a strong pace [2][8] - More than 120 clinical sites have been activated across 27 countries, all of which have received full regulatory approvals [2][8] - The first clinical site in the United States has received regulatory clearance following the FDA's Project Optimus initiative [3] Group 2: Future Milestones - The trial has already enrolled the necessary 170 patients for a futility analysis, which is expected to be conducted in the first quarter of CY2026 [4] - Completion of patient enrollment is anticipated in the third quarter of CY2026 [4] Group 3: Efti Overview - Efti is a first-in-class MHC Class II agonist that activates antigen-presenting cells to initiate a broad anti-cancer immune response [7] - Efti is being evaluated for various solid tumors, including non-small cell lung cancer, head and neck squamous cell carcinoma, soft tissue sarcoma, and breast cancer [8][9] Group 4: Company Background - Immutep is a late-stage biotechnology company focused on developing novel immunotherapies for cancer and autoimmune diseases, leveraging its expertise in LAG-3 therapeutics [10]

Core Insights - Immutep Limited is set to present new data from the AIPAC-003 trial at the 2025 San Antonio Breast Cancer Symposium, highlighting its late-stage immunotherapy targeting cancer and autoimmune diseases [1] Study Overview - The Phase II AIPAC-003 trial involved 66 female participants with HR+ and HER2-negative/HER2-low metastatic breast cancer resistant to endocrine therapy or metastatic triple-negative breast cancer not eligible for PD-(L)1 therapy [2] - Participants were randomized to receive either 30 mg or 90 mg of eftilagimod alfa in combination with paclitaxel to determine the optimal biological dose [2] Efficacy Results - The study reported strong objective response rates (ORR) of 41.9% for the 30 mg dose and 48.5% for the 90 mg dose, with disease control rates (DCR) of 87.1% and 78.8%, respectively [3] - Time to onset of response was similar at 2.0 months for the 30 mg dose and 1.9 months for the 90 mg dose [3] Pharmacodynamic Response - Both dosing levels showed significant increases in immune activation biomarkers, including absolute-lymphocyte count and interferon-gamma, aligning with the mechanism of action of eftilagimod alfa [4] Clinical Implications - The study's findings support the selection of 30 mg as the optimal biological dose, which is crucial for meeting FDA's Project Optimus requirements and advancing Immutep's oncology pipeline [6] - The ongoing Phase III TACTI-004 trial will evaluate eftilagimod alfa in combination with KEYTRUDA and chemotherapy for advanced or metastatic non-small cell lung cancer [6] Presentation Details - The presentation at SABCS 2025 will be led by Dr. Nuhad Ibrahim and will focus on the optimal biological dose of eftilagimod alfa in metastatic breast cancer patients [7][8]

Immutep Overview - Immutep has approximately A$109.85 million in cash and cash equivalents, providing a runway to the end of CY2026[14] - Immutep is developing four clinical-stage assets, including eftilagimod alfa (efti) and IMP761, designed to empower the immune system to fight cancer and autoimmune diseases[14] TACTI-004 (KEYNOTE-F91) Phase III Trial - The NSCLC drug market is expected to reach US$48 billion in sales in 2031[14,24] - The TACTI-004 Phase III trial has activated over 100 clinical sites across 24 countries and enrolled over 170 patients as of October 2025[25,30] - MSD is supplying KEYTRUDA for the TACTI-004 trial, with a typical ICI supply value of approximately US$100 million[30,32] Efficacy and Safety - In the INSIGHT-003 trial, a 62.7% objective response rate and a 90.2% disease control rate were observed across all PD-L1 expression levels in first-line NSCLC patients[52] - The EFTISARC-NEO trial in soft tissue sarcoma met its primary endpoint, demonstrating a median 51.5% tumor hyalinization/fibrosis rate (p<0.001) with neoadjuvant efti + KEYTRUDA + radiotherapy[52,70] Financials - Immutep's total revenue and other income were A$10.3 million in FY25, compared to A$7.8 million in FY24[79,80] - Research and development and intellectual property expenses increased to A$61.4 million in FY25[79,80] - The company reported a net loss of A$61.4 million in FY25[79] Intellectual Property - In FY24, seven patents were granted for efti, including six patents for efti in combination with a PD-1 pathway inhibitor[84] - Seven patents were granted for IMP761 in FY24[84] Anti-PD-(L)1 Therapies Sales - KEYTRUDA sales were approximately $29.5 billion in 2024[50,51] - OPDIVO sales were approximately $9.3 billion in 2024[50,51]

Core Insights - Immutep Limited announced positive results from the EFTISARC-NEO trial, demonstrating significant efficacy in treating resectable soft tissue sarcoma (STS) with a novel combination of eftilagimod alfa (efti), radiotherapy, and KEYTRUDA [1][2] Study Results - The Phase II study showed a median 51.5% tumor hyalinization/fibrosis in the evaluable patient population (N=38), significantly exceeding the prespecified pathologic response rates (p<0.001) [2] - The trial included patients with ten different STS subtypes, including aggressive tumors with poor prognosis such as myxofibrosarcoma (N=16) and undifferentiated pleomorphic sarcoma (N=10) [3] Immune Response - Early data indicated strong immune system activation, with significant increases in key cytokines and chemokines, including CXCL9 (2.5x, p<0.01), CXCL10 (1.8x, p<0.0001), IL-23 (2.2x, p<0.05), and IFN-γ (2.5x, p<0.05) [4][5] - The increase in immune response biomarkers correlated with pathologic responses, suggesting a higher probability of favorable clinical outcomes [5] Clinical Implications - The achieved tumor hyalinization/fibrosis rate is over three times greater than standard-of-care radiotherapy based on historical data, indicating potential for improved overall survival and recurrence-free survival in STS patients [6] - The findings support the hypothesis that efti's activation of antigen-presenting cells enhances both adaptive and innate immunity, which is crucial for effective cancer treatment [7][10] Future Directions - The results suggest that efti may have applications beyond advanced or metastatic cancer, potentially benefiting patients with localized and resectable tumors [10] - Ongoing translational studies aim to further explore the correlation between immune responses and clinical outcomes [6] Recognition - The EFTISARC-NEO trial received the Golden Scalpel Award in Poland, highlighting its innovation and impact in medical research and clinical practice [9][12] Company Overview - Immutep is a late-stage biotechnology company focused on developing novel immunotherapies for cancer and autoimmune diseases, leveraging its expertise in Lymphocyte Activation Gene-3 (LAG-3) [15]

Core Insights - Immutep Limited is advancing its clinical trials for eftilagimod alfa (efti) in oncology and autoimmune diseases, with significant progress reported in multiple trials [2][3][31] Oncology Development Programs - The TACTI-004 (KEYNOTE-F91) Phase III trial for advanced non-small cell lung cancer (NSCLC) is ongoing, with over 100 clinical sites activated across 24 countries, aiming to enroll approximately 756 patients [3][4] - The trial has successfully enrolled and randomized over 170 patients, surpassing the number required for a futility analysis, which is expected to be completed in Q1 CY2026 [6] - Positive feedback from the FDA has been received regarding the late-stage clinical development of efti for head and neck cancer patients with low PD-L1 expression [9][11] - The INSIGHT-003 Phase I trial is also evaluating efti in combination with KEYTRUDA® and chemotherapy for non-squamous NSCLC, with data presented at ESMO 2025 [7][8] Soft Tissue Sarcoma and Breast Cancer Trials - The EFTISARC-NEO Phase II trial for soft tissue sarcoma has met its primary endpoint, showing significant tumor hyalinization compared to historical data [16] - The AIPAC-003 trial for metastatic breast cancer has enrolled 71 patients, with ongoing follow-up and data analysis expected to be reported at the San Antonio Breast Cancer Symposium in December 2025 [17][19] Financial Position - As of September 30, 2025, Immutep reported a strong cash position of approximately A$109.85 million, consisting of A$83.41 million in cash and cash equivalents and A$26.44 million in term deposits [27] - The net cash used in R&D activities during Q1 FY26 was A$15.83 million, reflecting increased clinical trial activities [28] Intellectual Property Developments - Immutep was granted four new patents during the quarter, enhancing its intellectual property portfolio related to LAG-3 and its therapeutic applications [24]

Core Insights - Immutep Limited is focusing on changing the treatment paradigm for first-line non-small cell lung cancer (1L NSCLC) through innovative immunotherapy approaches [1][5]. Clinical Trial Results - The INSIGHT-003 trial demonstrated strong objective response rates (ORR) and disease control rates (DCR) for the combination of eftilagimod alfa (efti) with KEYTRUDA (pembrolizumab) and chemotherapy in patients with advanced or metastatic non-squamous 1L NSCLC [2][5]. - The ORR for patients with low and no PD-L1 expression (TPS <50%) reached 61.7%, significantly higher than the historical control of 40.8% [3][5]. - The combination therapy showed high ORR and DCR across all PD-L1 expression levels, with specific rates of 54.5% (no PD-L1), 68.0% (low PD-L1), and 75.0% (high PD-L1) [4]. Safety and Efficacy - The combination of efti with KEYTRUDA and chemotherapy has a favorable safety profile and has shown promising clinical responses, particularly in patients with low or absent PD-L1 expression [3][5]. - Efti is expected to set a new standard of care for 1L NSCLC patients, supported by data from multiple clinical trials, including the pivotal TACTI-004 Phase III trial [5][8]. Future Developments - The TACTI-004 Phase III trial is a global study enrolling approximately 756 patients with advanced/metastatic 1L NSCLC, evaluating the same immunotherapy/chemotherapy combination used in INSIGHT-003 [5][6]. - Efti is under evaluation for various solid tumors, including head and neck squamous cell carcinoma and breast cancer, and has received Fast Track designation from the FDA for first-line treatments [8]. Company Overview - Immutep is a late-stage biotechnology company specializing in novel immunotherapies for cancer and autoimmune diseases, leveraging its expertise in Lymphocyte Activation Gene-3 (LAG-3) [9].

Core Insights - Immutep Limited has received positive feedback from the FDA regarding the completion of Project Optimus and has agreed on 30mg as the optimal biological dose for eftilagimod alfa (efti) [1][2] Company Overview - Immutep is a late-stage biotechnology company focused on developing novel immunotherapies for cancer and autoimmune diseases, particularly leveraging Lymphocyte Activation Gene-3 (LAG-3) [5] Clinical Development - The agreement on efti's optimal biological dosing is strategically important for ongoing and future clinical development, including the TACTI-004 (KEYNOTE-F91) Phase III trial, which evaluates efti in combination with KEYTRUDA and chemotherapy for advanced or metastatic non-small cell lung cancer [2][4] - The TACTI-004 trial is currently in the process of opening clinical sites in the United States [7] Efti Overview - Efti is a novel immunotherapy that activates antigen-presenting cells via the MHC Class II pathway, engaging both the adaptive and innate immune systems to initiate a broad anti-cancer immune response [3] - Efti is being evaluated for various solid tumors, including non-small cell lung cancer, head and neck squamous cell carcinoma, soft tissue sarcoma, and breast cancer, and has received Fast Track designation from the FDA for first-line treatments in HNSCC and NSCLC [4]

Core Insights - Immutep Limited is advancing its TACTI-004 Phase III trial for eftilagimod alfa (efti) in combination with KEYTRUDA and chemotherapy for advanced non-small cell lung cancer (NSCLC) [1][4] Company Updates - The TACTI-004 trial has enrolled over 170 patients, surpassing the required number for a futility analysis [2][8] - There are now over 100 active clinical trial sites across 24 countries, indicating strong recruitment momentum [2][8] - The futility analysis is scheduled for the first quarter of CY2026, to be conducted by an independent data monitoring committee [3][8] Product Information - Efti is a first-in-class MHC Class II agonist that activates antigen-presenting cells to enhance anti-cancer immune responses [10][11] - The trial aims to enroll approximately 756 patients, focusing on those with advanced or metastatic NSCLC without specific genomic aberrations [7][9] Market Context - Lung cancer is the leading cause of cancer-related deaths, with an expected increase to approximately 3 million cases globally by 2030 [5] - NSCLC accounts for about 80-85% of lung cancer diagnoses, highlighting a significant unmet need for effective treatment options [5]

Core Viewpoint - Immutep Limited is advancing its clinical-stage biotechnology programs focused on LAG-3 immunotherapies for cancer and autoimmune diseases, with significant progress in multiple trials and a strong financial position as of June 30, 2025 [2][21]. Oncology Development Program - The TACTI-004 Phase III trial for advanced non-small cell lung cancer (NSCLC) is ongoing, with 78 sites across 23 countries activated for patient recruitment [3][4]. - The trial evaluates eftilagimod alfa (efti) in combination with KEYTRUDA® and chemotherapy, aiming to randomize approximately 756 patients [4]. - Immutep reported a 60.8% response rate and a 90.2% disease control rate in the INSIGHT-003 Phase I trial for non-squamous 1L NSCLC [6]. - In patients with TPS <50%, the triple combination achieved a 59.6% response rate compared to a historical control of 40.8% [7][8]. - The TACTI-003 Phase IIb trial for head and neck cancer showed a median overall survival of 17.6 months, outperforming historical standards of care [9][10]. - The EFTISARC-NEO Phase II trial for soft tissue sarcoma met its primary endpoint, significantly exceeding historical data for tumor hyalinization/fibrosis [12][13]. Autoimmune Disease Development Program - The Phase I trial of IMP761, a LAG-3 agonist antibody, demonstrated significant T cell suppression with a favorable safety profile at a dosing level of 0.9 mg/kg [16][17]. - Initial pharmacodynamic data indicated an 80% reduction in T cell activity, highlighting the potential efficacy of IMP761 in treating autoimmune diseases [18]. Intellectual Property - Immutep was granted four new patents during the quarter, including two for efti in combination with a PD-1 pathway inhibitor and two for IMP761 [19]. Corporate & Financial Summary - The company appointed Stephan Winckels as Chief Medical Officer, bringing over 15 years of oncology drug development experience [20]. - As of June 30, 2025, Immutep reported a cash position of approximately A$129.69 million, exceeding budget expectations [22]. - The net cash used in R&D activities during the quarter was A$15.66 million, reflecting increased clinical trial activities [23].

Core Insights - Immutep Limited is set to present the pivotal TACTI-004 Phase III trial at the IASLC 2025 World Conference on Lung Cancer, highlighting its focus on advanced non-small cell lung cancer treatment [1][2] Company Overview - Immutep is a late-stage biotechnology company specializing in immunotherapies for cancer and autoimmune diseases, particularly focusing on Lymphocyte Activation Gene-3 (LAG-3) [7] - The company aims to leverage its expertise to develop innovative treatment options and maximize shareholder value [7] Trial Details - The TACTI-004 Phase III trial evaluates the efficacy of Immutep's antigen presenting cell (APC) activator, eftilagimod alfa (efti), in combination with Merck's KEYTRUDA® and chemotherapy for first-line treatment of advanced or metastatic non-small cell lung cancer [2][4] - The trial will enroll approximately 750 patients across over 150 clinical sites in more than 25 countries, regardless of PD-L1 expression [2] Eftilagimod Alfa (efti) Profile - Efti is a first-in-class APC activator that stimulates both innate and adaptive immunity, enhancing the immune response against cancer [5] - It has a favorable safety profile and is being evaluated for various solid tumors, including non-small cell lung cancer, head and neck squamous cell carcinoma, and metastatic breast cancer [6] - Efti has received Fast Track designation from the FDA for first-line treatment in both head and neck squamous cell carcinoma and non-small cell lung cancer [6] Engagement with Medical Community - Immutep has received positive feedback from the lung cancer community regarding efti's safety and efficacy, indicating strong potential to change treatment paradigms for patients with advanced non-small cell lung cancer [3]